Reliable drug release➜➜ due to maximised surface

area (over 100 cm2 for 3 g ofmesalazine)

Even distribution throughout the colon➜ ➜ due to the large number

of pellets (3 g = approx. 3,500 pellets)

Administration independent of meals➜ ➜ as the pellets pass un-

hindered through the stomach (1mm diameter)

Mesalazine

OH

COOH

H2N

Easy to swallow and pleasant-tasting due to vanilla-flavoured film coating

2Continuous drug release Continuous drug release throughout the whole colon throughout the whole colon up to the rectum up to the rectum due to patented matrix core

Drug release starting in Drug release starting in the terminal ileum the terminal ileum due to pH-modified dissolution of the protective coating

Advantages over tablets

Innovative dual release technology for convincing efficacy also in distal ulcerative colitis

1

Salofalk®

Granules

Innovative dual release technology3 g once daily for treatment of acute ulcerative colitis

Continuous drug release throughout the colon up to the rectum

Salofalk® Granules 500mg/1000mg/1.5g; Salofalk® 250mg/500mg Gastro-resistant tablets, Salofalk® 250mg/500mg Suppositories, Salofalk® 2g/30ml and 4g/60ml Enemas; Salofalk® 1g Rectal Foam. Active ingredient: mesalazine (5-aminosalicylic acid). Composition: 1 sachet of Salofalk® granules 500mg/1000mg/1.5g contains: active ingredient: 500 mg/1000 mg/1.5 g mesalazine. Other ingredients: aspartame (E951), carmellose sodium, citric acid, silica colloidal anhydrous, hypromellose, magnesium stearate, methacrylic acid-methyl methacrylate copolymer (1:1) (Eudragit L 100), methylcellulose, cellulose microcrystalline, polyacrylate dispersion 40% (Eudragit NE 40 D containing 2% Nonoxynol 100), povidone K25, simeticone, sorbic acid, talc, titanium dioxide (E171), triethyl citrate, vanilla custard flavouring (containing propylene glycol). 1 tablet of Salofalk® 250mg/500mg contains: active ingredient: 250 mg/500 mg mesalazine. Other ingredients: Calcium stearate, basic butylated methacrylate copolymer (=Eudragit E), methacrylic acid methyl methacrylate copolymer (1:1) (=Eudragit L), glycine, silica colloidal anhydrous, hypromellose, macrogol 6000, cellulose microcrystalline, sodium carbonate anhydrous, povidone K25, talc. Colouring agents: titanium dioxide (E171), iron oxide hydrate (E172), additionally Salofalk® 500mg tablets: croscarmellose sodium. 1 Salofalk® 250mg/500mg suppository contains: active ingredient: 250 mg/500 mg mesalazine. Other ingredients: hard fat; additionally Salofalk® 500mg suppositories: docusate sodium, cetyl alcohol. 1 enema of Salofalk® 2g/30ml or 4g/60ml contains: active ingredient: 2 g or 4 g mesalazine. Other ingredients: sodium benzoate (E211), potassium metabisulphite (E224), potassium acetate, carbomer 947P, sodium edetate, xanthan gum, purified water. Note: Salofalk® enemas contain sodium benzo-ate and potassium metabisulphite. See patient information leaflet. Salofalk® 1g Rectal Foam: 1 actuation contains: active ingredient: 1 g mesalazine. Other ingredients: sodium metabisulphite(E223), cetostearyl alcohol, polysorbate 60, sodium edetate, propylene glycol. Propellants: propane, n-butane, isobutane. Note: Salofalk® 1g Rectal Foam contains sodium metabisulfite (E223), propylene glycol and cetostearyl alcohol. See patient information leaflet. Indications: Salofalk® granules 500mg/1000mg/1.5g: acute treatment and prevention of recurrence of ulcerative colitis (1.5g: only acute treatment). Salofalk® 250mg/500mg tablets: acute treatment and prevention of recurrence of inflammatory bowel disease (ulcerative colitis). Acute treatment of Crohn's disease (inflammatory bowel disease). Salofalk® 250mg/500mg suppositories: acute treatment of ulcerative colitis confined to the rectum. Additionally Salofalk® 250mg suppositories: preven-tion of recurrence (ulcerative colitis). Salofalk® 2g/30ml enemas: acute treatment of mild to moderate inflammatory bowel disease (ulcerative colitis), localised in the rectum and sigmoid colon. Salofalk® 4g/60ml enemas: acute treatment of inflammatory bowel disease (ulcerative colitis). Salofalk® 1g Rectal Foam: Treatment of active, mild ulcerative colitis of the sigmoid colon and rectum. Contraindications: existing hypersensitivity to salicylic acid, its derivatives or one of the other ingredients, severe liver and kidney function disturbances, gastric and duodenal ulcer, hemorrhagic diathesis. Children below the age of 6 years (Rectal Foam: Children below the age of 12 years). Pregnancy and lactation: risk-benefit ratio (only Rectal Foam: lactation). Additionally for Salofalk® enemas and Rectal Foam: not to be used in case of sensitive patients (especially for known asthmatics or allergic anamnesis) due to the content of potassium metabisulphite and sodium benzoate. Side effects: headaches, dizziness, peripheral neuropathy, abdominal pain, diarrhea, flatulence, nausea, vomiting, renal dysfunction including acute and chronic interstitial nephritis and renal failure, allergic exanthema, drug fever, bronchospasm, peri- and myocarditis, acute pancreatitis, allergic alveolitis, pancolitis, mesalazine-induced lupus erythematosus-like syndrome, myalgia, arthralgia, altered blood counts (aplastic anemia, agranulo-cytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia), changes in hepatic function parameters (increase in transaminases and pa-rameters of cholestasis), hepatitis, cholestatic hepatitis, alopecia (loss of hair), oligospermia. Additionally for Salofalk® enemas: hypersensitivity reactions in the form of irritations of skin, eyes and mucosa may be experienced in patients with allergic anamnesis due to the content of sodium benzoate. Additionally for Salofalk® 1g Rectal Foam: abdominal distension, anal discomfort, application site irritation, rectal tenesmus. Interactions:see patient information leaflet. Dosage: see patient information leaflet. Available on prescription only. Date of information: 01/2009 www.drfalkpharma.com

GranulesGranules

S13e

1-4

/200

9/5.

000

Rau

Optimised oral treatment Optimised oral treatment of distal colitisof distal colitis

(Data on file, Dr. Falk Pharma GmbH, Germany,Combined subgroup analysis of 4 pivotal, randomized, double-blind, controlled studies)

SalofalkSalofalk®®::Granules are significantly superior to Tablets Granules are significantly superior to Tablets

in distal ulcerative colitisin distal ulcerative colitis

Detailed information is given on the following page.

90

80

70

60

50

40

30

20

10

0

Patients in remission

[%]

Patients with active distal ulcerative colitis (proctosigmoiditis) in clinical remission at the end of the study [%]

78 %

55 %

3 g/day Salofalk® Granules

3 g/day Salofalk® Tablets

Treatment regime

Salofalk®

Granules

p < 0,0001

Study objectiveComparison of the efficacy of Salofalk® Granules and Salofalk® Tablets for induction of remission with regard to disease localisation in mildly-to-moderately active ulcerative colitis patients.

Study designCombined subgroup efficacy analysis from 4 pivotal, randomized, controlled phase III studies.

Patients705 patients suffering from active ulcerative colitis (Clinical Activity Index [CAI] > 4, Endoscopic Index >– 4) participating in the studies published by Kruis W, et al. Clin Gastro Hepatol 2003;1:36-43; Marakhouski Y, et al. Aliment Pharmacol Ther 2005;21(2):133-40; Kruis W, et al. Gut 2009; 58:233-40 or Gibson PR, et al. Aliment Pharmacol Ther 2006;23(7):1017-26.

Medication/study durationTreatment with 3 g mesalazine granules (Salofalk®; 3 g once daily (OD) or 1 g three-times daily (TID)) or 3 g mesalazine tablets (Salofalk®; 1g TID) for 8 weeks. Primary endpoint in all fours studies was clinical remission (CAI <– 4) at the final (week 8)/withdrawal visit.

ResultsIn mildly-to-moderately active, pan- and left-sided colitis, 3 g/day Salofalk®

granules induce remission comparable to that induced by a dosage of 3 g/day Salofalk® tablets (72 % vs. 71 % and 66 % vs. 67 %, p = n.s.). However, significantly more patients with distal disease achieved clinical remission with 3 g/day mesalazine granules compared to 3 g mesalazine tablets (78 % vs 55 %, p < 0,0001).

Clinical remission after 8 weeks

90

80

70

60

50

40

30

20

10

0

72 % 71 %66 % 67 %

Pancolitis Left-sided colitis

p = n.s. p = n.s.

Salofalk® Granules Salofalk® Tablets

78 %

55 %

Proctosigmoiditis

p < 0,0001

n = 116 n = 35 n = 158 n = 46 n = 257 n = 93